Orexin is required for brown adipose tissue development, differentiation, and function

Dyan Sellayah, Preeti Bharaj, Devanjan Sikder

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Orexin (OX) neuropeptides stimulate feeding and arousal. Deficiency of orexin is implicated in narcolepsy, a disease associated with obesity, paradoxically in the face of reduced food intake. Here, we show that obesity in orexin-null mice is associated with impaired brown adipose tissue (BAT) thermogenesis. Failure of thermogenesis in OX-null mice is due to inability of brown preadipocytes to differentiate. The differentiation defect in OX-null neonates is circumvented by OX injections to OX-null dams. In vitro, OX, triggers the full differentiation program in mesenchymal progenitor stem cells, embryonic fibroblasts and brown preadipocytes via p38 mitogen activated protein (MAP) kinase and bone morphogenetic protein receptor-1a (BMPR1A)-dependent Smad1/5 signaling. Our study suggests that obesity associated with OX depletion is linked to brown-fat hypoactivity, which leads to dampening of energy expenditure. Thus, orexin plays an integral role in adaptive thermogenesis and body weight regulation via effects on BAT differentiation and function.

Original languageEnglish (US)
Pages (from-to)478-490
Number of pages13
JournalCell Metabolism
Volume14
Issue number4
DOIs
StatePublished - Oct 5 2011
Externally publishedYes

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Brown Adipose Tissue
Thermogenesis
Obesity
Mesenchymal Stromal Cells
Bone Morphogenetic Protein Receptors
Narcolepsy
p38 Mitogen-Activated Protein Kinases
Arousal
Neuropeptides
Energy Metabolism
Fibroblasts
Eating
Body Weight
Injections

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Orexin is required for brown adipose tissue development, differentiation, and function. / Sellayah, Dyan; Bharaj, Preeti; Sikder, Devanjan.

In: Cell Metabolism, Vol. 14, No. 4, 05.10.2011, p. 478-490.

Research output: Contribution to journalArticle

Sellayah, Dyan ; Bharaj, Preeti ; Sikder, Devanjan. / Orexin is required for brown adipose tissue development, differentiation, and function. In: Cell Metabolism. 2011 ; Vol. 14, No. 4. pp. 478-490.
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